Two antifungal phenyl-phenalenone phytoalexins isolated from the banana plant (Musa acuminata) elicited with the fungus Fusarium oxysporum, together with a methoxy derivative of one of them and two epoxide precursors of their chemical synthesis, were tested for leishmanicidal activity on Leishmania donovani promastigotes and L. infantum amastigotes. Drugs inhibited proliferation of both forms of the parasite with a 50% lethal concentration range between 10.3 and 68.7 g/ml. Their lethal mechanism was found linked to the respiratory chain by a systematic approach, including electron microscopy, measurement of the oxygen consumption rate on digitonin-permeabilized promastigotes, and enzymatic assays on a mitochondrial enriched fraction. Whereas the whole set of compounds inhibited the activity of fumarate reductase in the mitochondrial fraction (50% effective concentration [EC 50 ] between 33.3 and 78.8 g/ml) and on purified enzyme (EC 50 ؍ 53.3 to 115 g/ml), inhibition for succinate dehydrogenase was only observed for the two phytoalexins with the highest leishmanicidal activity: anigorufone and its natural analogue 2-methoxy-9-phenyl-phenalen-1-one (EC 50 ؍ 33.5 and 59.6 g/ml, respectively). These results provided a new structural motif, phenyl-phenalenone, as a new lead for leishmanicidal activity, and support the use of plant extracts enriched in antifungal phytoalexins, synthesized under fungal challenge, as a more rational and effective strategy to screen for new plant leishmanicidal drugs.
Four new phenalenone-type phytoalexins (2 -5) have been isolated from rhizomes of Musa acumituzta (AAA) infected with the fungus Fusurium oxysporum. The structures of the new phytoalexins were elucidated using spectroscopic evidence, chemical correlation, synthesis, and X-ray diffraction analysis. The major compound 2, has been previously described as a natural product, named anigorufone, but never as a phytoalexin. The chemical shift for all of the hydrogen and carbon atoms in the substances were unanibiguously established by mono-and bidimensional, homo-and heteronuclear NMR experiments ('HNMR, ''CNMR, COSY, HMQC and HMBC). In preliminary in virro assays, all of the four new phytoalexins have shown inhibitory activity on the growth of the germinative tube of Fusurium oxysporum f. sp. cubense race 4.
The isolation and characterisation of (S)-(+)-6-methoxy-alpha-methyl-2-naphthaleneacetic acid, a well known synthetic non-steroidal anti-inflammatory drug (naproxene), from a natural source is described for the first time. We evaluated the ability of naproxene and its 7-methoxy isomer to abrogate constitutive COX-1 and inducible COX-2 activity in human A549 cells. Naproxene inhibited COX-1 (IC50 = 3.42 microM) and COX-2 (IC50 = 1.53 microM), whereas the 7-methoxy isomer had no appreciable effect on COX-1 (IC50 >> 100 microM) but also abrogated the activity of COX-2 enzyme (IC50 = 14.42 microM).
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